The relative amounts of the collagen chains alpha 1(I), alpha 2 and alpha 1(III) in the skin of 31 patients with osteogenesis imperfecta.
1. The relative amounts of type III and type I collagen, determined as the ratio of their constituent alpha 1(III) and alpha 1(I) chains, have been measured by interrupted electrophoresis of pepsin extracts of skin collagen from 31 patients with osteogenesis imperfecta of varying severity, and from six clinically unaffected family members. In 18 patients the ratio of the alpha 1(I) to alpha 2 chains of type I collagen has also been measured. 2. In the 15 patients with osteogenesis imperfecta classified as mild or the 18 with type I disease the ratio alpha 1(III)/alpha 1(I) was significantly increased (P less than 0.001) and the ratio alpha 1(I)/alpha 2 significantly decreased (P less than 0.005) compared with age-matched control subjects. 3. In three infants with lethal (type II) osteogenesis imperfecta the ratio alpha 1(III)/alpha 1(I) was normal, contrasting with the high ratio observed by others in fibroblast cultures from some apparently similar patients. 4. The ratio of alpha 1(I)/alpha 2 and of alpha 1(III)/alpha 2(I) was increased in both clinically normal parents of a child with severe disease, and in the mother of two children with osteogenesis imperfecta (one lethal and one severe) the ratio alpha 1(III)/alpha 1(I) was increased. 5. In the remaining patients with severe bone deformity (types III and IV) the relative amounts of the different collagen chains varied. 6. These data support previous suggestions that mild or type I osteogenesis imperfecta results from a generalized inability to form sufficient type I collagen, the predominant collagen of adult bone, and imply that in many cases this may result from defective production of the alpha 1(I) chain rather than of the alpha 2 chain. Some patients with severe disease demonstrate a similar defect; but in the remainder other abnormalities of collagen or connective tissue maturation are presumably involved.
D000293:Adolescent; D000328:Adult; D002648:Child; D003094:Collagen / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008875:Middle Aged; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010434:Pepsin A; D010446:Peptide Fragments / Q000032:analysis; D012867:Skin / Q000032:analysis*
D010446:Peptide Fragments; D003094:Collagen; D010434:Pepsin A